Heart failure (HF) involves an impairment in the ability of the heart to fill with and/or eject blood. Regardless of etiology, HF is associated with the accumulation of connective tissue termed “reactive interstitial fibrosis” in the interstitial compartment of the myocardium. Interstitial fibrosis can, in turn, have an adverse impact on the myocardium by 1) increasing oxygen diffusion distance and, therefore, lead to myocardial hypoxia; 2) reducing capillary density and, therefore, influence coronary perfusion and 3) increasing myocardial stiffness (reduce compliance) and, in doing so, reduce left ventricular relaxation and filling, and increase myocardial oxygen consumption. Reducing the burden of interstitial fibrosis, therefore, is a key therapeutic goal in HF.
While many therapies exist for treating systolic HF, the disease continues to claim the lives of many Americans and people worldwide. Even with optimal medical therapy, once diagnosed, systolic HF progressively worsens. Patients with advanced HF have a mortality rate of nearly 50% per year. Diastolic HF is a condition whereby the patient develops all the symptoms of systolic HF except that the systolic function of the left ventricle is not depressed, as is typical of systolic HF. In contrast to systolic HF, there are no known therapies for diastolic HF, even though this form of the disease affects nearly 40% of the entire HF population which, in the US, is nearly 6 million people. Identifying effective therapies to treat diastolic HF is a major unmet need in the United States and worldwide.